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Trial registered on ANZCTR


Registration number
ACTRN12617001055392
Ethics application status
Approved
Date submitted
28/06/2017
Date registered
19/07/2017
Date last updated
5/11/2019
Date data sharing statement initially provided
5/11/2019
Date results information initially provided
5/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and safety of artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Jowhar and Bosaso sites, Somalia.
Scientific title
Efficacy and safety of artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Jowhar and Bosaso sites, Somalia.
Secondary ID [1] 292279 0
None
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 303797 0
Condition category
Condition code
Infection 303166 303166 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The objective of the study is to assess the efficacy and safety of artemether+lumefantrine (20 mg/120 mg in each table) twice daily doses for three days for the treatment of uncomplicated falciparum malaria. The dose will be calculated based on the recommended weight bands as follows: 1 tablet to those weighing 5 to 14 kg; 2 tablets for 15 to 24 kg; 3 tablets for 25 to 34 kg and 4 tablets for equal or greater than 35 kg.

All treatments will be taken orally under direct supervision by the health worker and will be followed up for 28 days.
Intervention code [1] 298452 0
Treatment: Drugs
Comparator / control treatment
No comparator
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302537 0
Percent of treatment failures (early treatment failure + late clinical failure +late parasitological failure). This is composite primary outcome.

Enrolled patients will be assessed for parasitological and clinical responses during the 28 days follow-up and treatment outcomes will be classified according to the latest WHO protocol.
Timepoint [1] 302537 0
Days 1, 2, 3, 7, 14, 21, 28
Secondary outcome [1] 336333 0
Percent of adverse event following treatment of each drugs will be documented.
The known adverse events of:

Atemether+lumefantrine are abdominal pain, asthenia, cough, diarrhoea, dizziness, fever, headache, joint and muscle pain, loss of appetite, rush, nausea, vomiting.
Parents or guardians of all enrolled children will be asked routinely about previous symptoms and about symptoms that have emerged since the previous follow-up visit. When clinically indicated, patients will be evaluated and treated appropriately. All adverse events will be recorded on the case report form.
Timepoint [1] 336333 0
Days 1, 2, 3, 7, 14, 21, 28
Secondary outcome [2] 336334 0
Prevalence of artemisinin resistance molecular markers (K13).
Parasite DNA extracted from the dried blood spots will be analyzed by PCR and sequencing for the presence of K13 (molecular marker for artemisinin resistance).
Timepoint [2] 336334 0
Day 0

Eligibility
Key inclusion criteria
1. age between 6 months and 60 years with the exception of 12-17years old female minors and unmarried females 18 years and above;
2. mono-infection with P. falciparum detected by microscopy;
3. parasitaemia of 500 - 200000/µl asexual forms;
4. presence of axillary or tympanic temperature greater or equal to 37.5 degree centigrade or history of fever during the past 24 h;
5. ability to swallow oral medication;
6. ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule;
7. informed consent from the patient or from a parent or guardian in the case of children aged less than 18 years;
8. informed assent from any minor participant aged from 12 to age of majority years; and
9. consent for pregnancy testing from married female of 18 years and above.
Minimum age
6 Months
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO;
2. weight under 5 kg;
3. mixed or mono-infection with another Plasmodium species detected by microscopy;
4. presence of severe malnutrition (defined as a child aged 6-60 months who has a mid-upper arm circumference below 115 mm);
5. presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
6. regular medication, which may interfere with antimalarial pharmacokinetics;
7. history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s);
8. a positive pregnancy test or breastfeeding of married women aged 18 years and above; and
9. unable to or unwilling to take pregnancy test or to use contraception for women of child-bearing age and who are sexually active.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
No concealment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size
As the treatment failure rate to artemether+lumefantrine in the areas is estimated to 5%. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 73 patients will be included. With a 20% increase to allow loss to follow-up and withdrawals during the 28-day follow-up period, 88 patients per site will be included in the study.

Analysis of data
The WHO excel software programs will be used for data management and analysis. Data will be analysed by two methods: the Kaplan-Meier method and per-protocol analysis. In addition to the reasons for withdrawal listed in section 3.8, patients will be considered withdrawn from the analysis if the PCR results are unclassifiable or if the results of PCR indicate that the failure is due to reinfection with P. falciparum or P. vivax.

The final analysis will include:

1. a description of all patients screened and the distribution of reasons for non-inclusion in the study;
2. a description of all the patients included in the study;
3. the proportion of adverse events and serious adverse events in all the patients included in the study;
4. the proportion of patients lost to follow-up or withdrawn, with 95% confidence intervals and a list of reasons for withdrawal;
5. the cumulative incidence of success and failure rates at day 28, PCR-uncorrected and PCR-corrected; and
6. the proportion of early treatment failure, late clinical failure, late parasitological failure and adequate clinical and parasitological response at day 28, with 95% confidence intervals, PCR-uncorrected and PCR-corrected.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2017
Actual
21/08/2017
Date of last participant enrolment
Anticipated
30/03/2018
Actual
20/02/2018
Date of last data collection
Anticipated
30/04/2018
Actual
20/03/2018
Sample size
Target
176
Accrual to date
Final
139
Recruitment outside Australia
Country [1] 9015 0
Somalia
State/province [1] 9015 0
Middle Shabelle and North East Region

Funding & Sponsors
Funding source category [1] 296821 0
Other
Name [1] 296821 0
World Health Organization
Country [1] 296821 0
Somalia
Primary sponsor type
Government body
Name
Ministry of Health and Human Services, Federal Government
Address
Mogadihsu Somalia
Country
Somalia
Secondary sponsor category [1] 295810 0
None
Name [1] 295810 0
Address [1] 295810 0
Country [1] 295810 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298056 0
WHO ERC
Ethics committee address [1] 298056 0
20 Av. Appia,
1211 Geneva 27 Switzerland
Ethics committee country [1] 298056 0
Switzerland
Date submitted for ethics approval [1] 298056 0
25/05/2017
Approval date [1] 298056 0
15/06/2017
Ethics approval number [1] 298056 0
ERC.0002915

Summary
Brief summary
Title: Efficacy and safety of artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Johar and Bosaso sites, Somalia.
Purpose: To assess the efficacy of a potential second line treatment policy.
Objective: To assess the efficacy and safety of artemether+lumefantrine for the treatment of uncomplicated P. falciparum malaria infections.
Study Sites: Johar and Bosaso sites.
Study Period: From August 2017 to April 2018
Study Design: One arm prospective study.
Patient population: Febrile patients aged between 6 months and 60 years, inclusive, with confirmed uncomplicated P. falciparum infection. Female minors aged 12-17 years and unmarried females aged 18 years and above will be excluded as subjecting them to pregnancy testing is unacceptable according to the local customs and cultures.
Sample Size: A total of 88 patients will be enrolled in each site.
Treatment(s) and follow-up: Artemether+lumefantrine twice daily for 3 days will be evaluated. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy.
Primary endpoints: The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis.
Secondary endpoints:
1. The frequency and nature of adverse events
2. proportion of polymorphism of molecular markers for artemisinin resistance (K13)
Trial website
Nil
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75842 0
Mr Abdullahi Mohamed Hassan
Address 75842 0
Minitry of Health and Human Services
Wadajir, Km5, Zope Street
Mogadishu
Country 75842 0
Somalia
Phone 75842 0
+252615500514
Fax 75842 0
Email 75842 0
[email protected]
Contact person for public queries
Name 75843 0
Abdullahi Mohamed Hassan
Address 75843 0
Minitry of Health and Human Services
Wadajir, Km5, Zope Street
Mogadishu
Country 75843 0
Somalia
Phone 75843 0
+252615500514
Fax 75843 0
Email 75843 0
[email protected]
Contact person for scientific queries
Name 75844 0
Marian Warsame
Address 75844 0
20 Av. Appia,
1211 Geneva 27 Switzerland
Country 75844 0
Switzerland
Phone 75844 0
+41227915076
Fax 75844 0
Email 75844 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Warsame M, Hassan AM, Hassan AH, Jibril AM, Khim N... [More Details] 373196-(Uploaded-31-10-2019-23-18-29)-Journal results publication.pdf

Documents added automatically
No additional documents have been identified.